The MITF p.E318K pathogenic variant (PV) is well-established as a melanoma risk factor and has been proposed as a genetic risk factor for renal cell carcinoma (RCC). The initial report of RCC in individuals with MITF p.E318K was published in 2011 based on a French population that suggested a fivefold increased risk of developing melanoma, RCC or both cancers.1 In 2024, Harraka et al provided a summary of prior work evaluating the association between MITF p.E318K and RCC risk and concluded the findings have been inconsistent to date.2 Large-scale biobank analyses were recently completed by Walker et al who found no significant association between MITF p.E318K and RCC.3 The strength of conclusions from many of the prior datasets has been limited by lack of access to robust personal and family history in determining if patients with MITF p.E318K have an elevated risk of RCC….
